Cofactor recovery is one of the major hurdles of cofactor-dependent enzyme-catalyzed reactions. The development of easily recoverable reversibly soluble form of nicotinamide cofactors is the focus of this proposal. The idea consists of the cofactor modification with reversibly soluble polymers. Consequently, the cofactor can be dissolved again in a solution or suspension of the starting materials at the initial conditions. Therefore, these cofactors acquire the advantages of permanently soluble cofactors (high activity both in homogeneous and heterogeneous systems) and of immobilized cofactors (easy recovery). Today, there are no reversibly soluble cofactors on the market. Potential of the idea was demonstrated during preliminary studies. Phase I of the proposal focuses on the choice of the best method to synthesize thermo- and pH responsive reversibly soluble cofactors. Optimization of their synthesis, development of the proprietary technology to manufacture chiral pharmaceuticals using reversibly soluble cofactors will be the goals of Phase II. There are no patents either on the synthesis of reversibly soluble cofactors or their use for synthesis. Reversibly soluble cofactors and chiral compounds will be marketed to pharmaceutical companies. In 2000, total market for chiral compounds reached $4 billion. PROPOSED COMMERCIAL APPLICATIONS: Reversibly soluble cofactors are unique because they combine advantages of soluble and immobilized cofactors. There are no cofactors of this kind commercially available. They will be used internally at Polium Technologies and sold to pharmaceutical companies to manufacture chiral intermediates. Market for chiral intermediates is about $4 billion per year. Sales of intermediates for a production of just one drug can bring several million annually.